Michael addition reactions with η2-coordinaied anisoles: Controlling the stereochemistry of the para and benzylic carbons

Article abstract of DOI:10.1021/ja047054j

Several η²-coordinated anisole complexes were treated with various Michael acceptors in the presence of a Lewis or Br?nsted acid to generate stable 4H-anisolium complexes. These reactions were found to proceed with high stereochemical control with predictable outcomes, provided that the moderate acid (NH₂Ph₂)OTf was used and the complex was dissolved in an acidic solution. The stereochemistry is shown to originate from an unexpectedly high preference for one coordination diastereomer of the anisole complex in the solid state and a Diels-Alder like transition state for the Michael reaction.

Full text of DOI:10.1021/ja047054j

Published on Web 11/09/2004
Michael Addition Reactions with η2-Coordinated Anisoles:
Controlling the Stereochemistry of the Para and
Benzylic Carbons
Philip L. Smith, Joseph M. Keane, Sarah E. Shankman, Mahendra D. Chordia, and
W. Dean Harman*
Contribution from the Department of Chemistry, UniVersity of Virginia, P.O. 400319,
CharlottesVille, Virginia 22904-4319
Received May 19, 2004; E-mail: wdh5z@virginia.edu
Abstract: Several η2-coordinated anisole complexes were treated with various Michael acceptors in the
presence of a Lewis or Brønsted acid to generate stable 4H-anisolium complexes. These reactions were
found to proceed with high stereochemical control with predictable outcomes, provided that the moderate
acid (NH2Ph2)OTf was used and the complex was dissolved in an acidic solution. The stereochemistry is
shown to originate from an unexpectedly high preference for one coordination diastereomer of the anisole
complex in the solid state and a Diels-Alder like transition state for the Michael reaction.
Introduction
An alternative approach to arene alkylation relies on coor-
dination of the arene to a transition metal.12-14 In particular,
our focus has been on arene transformations facilitated by η2-
coordination to a π-basic metal fragment. Significant π-electron
donation from the metal to the bound arene renders the arene
more nucleophilic and vastly expands the scope of reactions to
which the arene is susceptible.14 While the pioneering work in
The alkylation of arenes is an important process that continues
to receive a great deal of study. Of particular interest to
medicinal chemists are those reactions that allow for stereo-
control at newly formed benzylic centers.1,2 While Friedel-
Crafts and related methodologies remain mainstays of organic
synthesis,3,4 they are typically plagued by a variety of problems,
including multiple additions, poor regioselectivity, and harsh
reaction conditions. These problems are avoided by approaches
that involve metal coupling reagents, but most such reactions
require prior functionalization (typically halogenation) of the
arene reaction site.5-8 Recently, some intriguing results have
been reported on the application of arene C-H activation studies
to C-C bond formation,9-11 and investigations that extend the
scope of this chemistry may result in effective alkylation
strategies.
this area was carried out with pentaammineosmium(II),15-17
a
new series of dearomatizing metal fragments having the general
form {TpM(π-acid)(L)} [Tp ) hydridotris(pyrazolyl)borate, M
) rhenium, molybdenum, or tungsten, π-acid ) CO or NO,
and L ) a variable ligand] has recently been developed.18-23
Some members of this series have demonstrated a greater ability
than osmium(II) to activate aromatic molecules toward reaction
with electrophiles.23,24 Perhaps of greater significance, the
(12) Pape, A. R.; Kaliappan, K. P.; Ku¨ndig, E. P. Chem. ReV. 2000, 100, 2917-
2940.
(13) Semmelhack, M. F. In ComprehensiVe Organometallic Chemistry II; Abel,
E. W., Stone, F. G. A., Wilkinson, G., Eds.; Pergamon Press: Oxford,
UK, 1995; Vol. 12, pp 979-1015.
(1) Paras, N. A.; Macmillan: D. W. C. J. Am. Chem. Soc. 2002, 124, 7894-
7895.
(14) Ku¨ndig, E. P. Transition Metal Arene π Complexes in Organic Synthesis
and Catalysis; Springer-Verlag: Berlin, 2004.
(2) Saaby, S.; Bayon, P.; Aburel, P. S.; Jorgenson, K. A. J. Org. Chem. 2002,
67, 4352-4361.
(15) Kopach, M. E.; Gonzalez, J.; Harman, W. D. J. Am. Chem. Soc. 1991,
113, 8972-8973.
(3) Heaney, H. ComprehensiVe Organic Synthesis; Pergamon Press: Oxford,
1991; Vol. 2.
(16) Kolis, S. P.; Kopach, M. E.; Liu, R.; Harman, W. D. J. Org. Chem. 1997,
62, 130-136.
(4) Olah, G. A.; Krishnamurti, R.; Prakash, G. K. S. 1991, 3, 293-339.
(5) Knight, D. W. ComprehensiVe Organic Chemistry; Pergamon Press:
Oxford, 1991; Vol. 3.
(17) Harman, W. D. Chem. ReV. 1997, 97, 1953-1978.
(18) Gunnoe, T. B.; Sabat, M.; Harman, W. D. J. Am. Chem. Soc. 1999, 121,
6499-6500.
(19) Gunnoe, T. B.; Sabat, M.; Harman, W. D. Organometallics 2000, 19, 728-
740.
(6) Tamao, K. ComprehensiVe Organic Chemistry; Pergamon Press: Oxford,
1991; Vol. 3.
(7) Miyaura, N. S.; Akira, Chem. ReV. 1995, 95, 2457-2483.
(8) Beletskaya, I. P. C.; Andrei, V. Chem. ReV. 2000, 100, 3009-3066.
(9) Jia, C.; Lu, W.; Oyamada, J.; Kitamura, T.; Matsuda, K.; Irie, M.; Fujiwara,
Y. J. Am. Chem. Soc. 2000, 122, 7252-7263.
(20) Meiere, S. H.; Brooks, B. C.; Gunnoe, T. B.; Sabat, M.; Harman, W. D.
Organometallics 2001, 20, 1038-1040.
(21) Meiere, S. H.; Brooks, B. C.; Gunnoe, T. B.; Carrig, E. H.; Sabat, M.;
Harman, W. D. Organometallics 2001, 20, 3661-3671.
(22) Meiere, S. H.; Keane, J. M.; Gunnoe, T. B.; Sabat, M.; Harman, W. D. J.
Am. Chem. Soc. 2003, 125, 2024-2025.
(10) Jia, C.; Piao, D.; Oyamada, J.; Lu, W.; Kitamura, T.; Fujiwara, Y. Science
2000, 287, 1992-1995.
(11) Murai, S.; Kakiuchi, F.; Sekine, S.; Tanaka, Y.; Kamatani, A.; Sonoda,
M.; Chanati, N. Nature 1993, 366, 529-531.
(23) Graham, P.; Meiere, S. H.; Sabat, M.; Harman, W. D. Organometallics
2003, 22, 4364-4366.
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A R T I C L E S
Smith et al.
stereogenic metal is able to differentiate enantiofaces of the η2-
arene.
Scheme 1. Two Michael Addition Reactions of
TpRe(CO)(MeIm)(5,6-η2-anisole) (1)
reaction ii). In a typical reaction sequence, the arene complex
and Michael acceptor were combined and cooled (-10 °C for
reactions with Sc(OTf)3 or -40 °C for that with TBSOTf), and
then the Lewis acid was added at low temperature. The resulting
4H-anisolium complexes were isolated by precipitation into
Et2O/hexanes (1:1). Results for the reactions of 1, 2, and 3 with
various Michael acceptors are summarized in Table 1. Yields
of the resulting anisolium salts (5-16) were high, but the purity
of these compounds, as determined by combustion analysis, was
found to be unsatisfactory, presumably due to residual Lewis
acid and decomposition products (vide infra). While the facial
diastereoselectivity of the products (A:B) reflected the low
diastereomeric ratio of the initial solvated anisole complexes,
significant diastereocontrol at the latent benzylic position (endo:
exo, vide infra) was observed in several examples.
During the course of investigations of cycloaddition reactions
of {TpRe(CO)(MeIm)(η2-anisole)} and dienophiles,24 an over-
whelming preference for Michael-type additions over cycload-
ditions was observed when the reactions were performed under
Lewis-acidic reaction conditions. Given the greater electron-
donating ability of the {TpRe(CO)(MeIm)} fragment, it was
hoped that these complexes would react under milder conditions
than those used with pentaammineosmium(II) anisoles. Fur-
thermore, in consideration of the chiral ligand environment for
this rhenium system, we hoped to develop a strategy for
controlling the absolute stereochemistry for these Michael
addition reactions.
Results
The extremely low solubility of the {TpRe(CO)(MeIm)}
anisole complexes in a variety of common organic solvents has
been previously documented.28 In the current study, this low
solubility led to difficulty obtaining complete conversion in the
synthesis of TpRe(CO)(MeIm)(5,6-η2-anisole) (1), TpRe(CO)-
(MeIm)(5,6-η2-(3-methylanisole)) (2), and TpRe(CO)(MeIm)-
(5,6-η2-(3-methoxyanisole)) (3) and limited the range of reaction
solvents in which these complexes could be dissolved. (The
above investigations were typically carried out in solutions of
THF and methylene chloride). For these reasons, further
investigations were carried out using the TpRe(CO)(BuIm)(5,6-
η2-anisole) (4) analogue. The greater solubility of the N-
butylimidazole variant (4) allowed for both facile preparations
of pure samples and a much wider range of reaction solvent
conditions.
During the course of protonation studies with the TpRe(CO)-
(RIm)(η2-anisole) complexes, we discovered that moderately
strong Brønsted acids such as protonated alcohols or arylam-
monium salts could be used to form anisolium complexes with
good stereocontrol (A:B).28 It was hypothesized that a moderate
acid could be used to reversibly capture one coordination
diastereomer of the anisole complex (as a 2H-anisolium) and
then to promote a Michael addition reaction at a sufficiently
high rate that the stereochemistry of coordination is conserved
(Scheme 2).
In an initial study, TpRe(CO)(MeIm)(5,6-η2-anisole) (1),
TpRe(CO)(MeIm)(5,6-η2-(3-methylanisole)) (2), and TpRe-
(CO)(MeIm)(5,6-η2-(3-methoxyanisole)) (3) were screened with
various Michael acceptors and Lewis acids under a variety of
reaction conditions. Attempts to promote the model reaction of
TpRe(CO)(MeIm)(η2-anisole) (1) and MVK with triflic acid in
acetonitrile (20 to -60 °C) caused rapid decomposition of the
complex, yielding only traces of the 4H-anisolium product, while
Zn(II), Yb(III), Ti(IV), Sn(II), anhydrous Sc(OTf)3, or TBSOTf
(with MVK and other conjugated ketones) resulted in either no
reaction, oxidation, or intractable mixtures of products. The use
of BF3‚OEt2 was more promising, with varying amounts of the
desired addition product being observed along with other
unidentified material. However, compounds 1-3 were found
to readily undergo conjugate addition reactions with a number
of R,â-unsaturated carbonyl compounds in the presence of either
Sc(OTf)325-27 or TBSOTf. For N-methylmaleimide and conju-
gated ketones, wet Sc(OTf)3 promoted conjugate addition and
protonation of the resulting enolate to afford 4H-anisolium
complexes (e.g., Scheme 1, reaction i). Similarly, the less
reactive electrophile methyl acrylate reacted when TBSOTf was
employed, yielding the 4H-anisolium complex 16 (Scheme 1,
(24) Chordia, M. D.; Smith, P. L.; Meiere, S. H.; Sabat, M.; Harman, W. D. J.
Am. Chem. Soc. 2001, 123, 10756-10757.
(25) Kobayashi, S.; Hachiya, I.; Ishitani, H.; Araki, M. Synlett 1993, 472-474.
(26) Kobayashi, S. Synlett 1994, 689-701.
(28) Keane, J. M.; Chordia, M. D.; Mocella, C. J.; Sabat, M.; Trindle, C. O.;
(27) Kobayashi, S. Eur. J. Org. Chem. 1999, 15-27.
Harman, W. D. J. Am. Chem. Soc. 2004, 126, 6806-6815.
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Michael Addition with
η
2-Coordinated Anisoles
A R T I C L E S
Table 1. Michael Additions of {TpRe(CO)(MeIm)} Anisole Complexes
1
a The diastereomeric ratio A:B in the isolated anisolium products as determined by H NMR. b Stereoselectivity at the benzylic carbon regardless of the
orientation of the ligand with respect to the metal fragment; in each case, the major isomer is thought to have an endo-configuration, but this outcome has
been confirmed only for complex 14. c The overall yield of the net aromatic substitution product from arene complex 1, 2, or 3.
Indeed, when solutions of various Michael acceptors were
diphenylammonium triflate, additions occurred to give highly
diastereoselective anisolium products that could be isolated, in
high yields and in analytically pure forms, by precipitation into
hexanes following aqueous extraction. Results for reactions of
4 with various Michael acceptors are detailed in Table 2. Facial
diastereoselectivity of anisolium complexes 29-33 was uni-
formly high (>20:1 A:B), as long as the initial complexes were
dissolved in the presence of the acid. Alternatively, when TpRe-
(CO)(BuIm)(5,6-η2-anisole) (4) was first dissolved at ambient
temperature and then exposed to acid and cyclopenten-2-one,
the resulting anisolium (31) showed only 4:1 diastereoselectivity
(A:B).
added to mixtures of TpRe(CO)(BuIm)(5,6-η2-anisole) (4) and
Scheme 2. Mechanism Proposed To Be Responsible for the High
Degree of Facial Diastereoselectivity (A:B) Observed in Anisolium
Products 29-33
Spectroscopic features of {TpRe(CO)(RIm)} 4H-anisolium
complexes 5-16 and 29-33 include bound olefinic resonances
that appear as broad doublets (JHH ) 7.5) between 3.4 and 5.0
1
ppm in the H NMR spectrum. The 13C NMR spectra of these
complexes feature resonances at ∼187 ppm (C1), ∼70 ppm
(C5), and ∼60 ppm (C6). Facial diastereomers of 5-16 and
29-33 (A:B) were assigned on the basis of established trends
in the chemical shifts of protons at the bound positions.20,21,24
These assignments are supported by a one-dimensional NOE
study of [TpRe(CO)(MeIm)(4â-(2-(methoxycarbonyl)ethyl)-
5R,6R-η2-(4H-anisolium))](OTf) (16) (Figure 1). Irradiation of
the downfield oxonium methoxy protons of diastereomer A (δ
3.55) resulted in enhancement of two imidazole resonances,
whereas irradiation of the upfield oxonium methoxy protons of
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A R T I C L E S
Smith et al.
Table 2. Michael Additions of TpRe(CO)(BuIm)(5,6-η2-anisole) (4)
a Yield of the isolated anisolium complex from 4. b The diastereomeric ratio A:B in the isolated anisolium products as determined by 1H NMR.
c Stereoselectivity at the benzylic carbon regardless of the orientation of the ligand with respect to the metal fragment; in each case, the major isomer is
thought to have an endo-configuration, but this outcome has been confirmed only for complex 14. d The overall yield of the net aromatic substitution product
from arene complex 4.
transition state arrangement of the Michael acceptor with respect
to the unbound portion of the aromatic ring (vide infra). The
alternative configuration is designated as exo. An authentic
sample of 14-endo was prepared through an acid-promoted
retro-Aldol type ring-opening of the N-methylmaleimide cy-
cloadduct of TpRe(CO)(MeIm)(5,6-η2-anisole) (1) (complex 35,
1
vide infra; Scheme 3). The H NMR spectra of the Michael
addition product assigned as 14-endo matched that of an
authentic sample.
Anisolium complexes 5-16 and 29-33 were found to be
unstable to silica and alumina, but they were stable to water
and more resistant to thermal degradation than the previously
reported pentaammineosmium(II) analogues.16 The {TpRe(CO)-
(RIm)}-bound anisoliums remained intact for several weeks
when stored as solids at ambient temperature. When samples
of 5-16 and 29-33 were allowed to stand in solution at ambient
temperature, the formation of 4-alkylanisoles was typically
observed over a period of days. Remarkably, the rate of
formation of 17-28 and 34 was not significantly affected by
the presence of amine bases such as DIEA or pyridine, indicating
Figure 1. Data used to assign the A:B isomers of [TpRe(CO)(MeIm)(4â-
a high kinetic barrier for deprotonation at C4. The use of
stronger bases such as NaH, NaOMe, and LiHMDS resulted in
(2-(methoxycarbonyl)ethyl)-5R,6R-η2-(4H-anisolium))](OTf) (16).
retro-Michael reactions, from which the parent anisole com-
plexes were isolated. Oxidation using CuBr2 proved to be an
effective strategy for decomplexation with concomitant rearo-
matization. Exposure to air, heat, trifluoroacetic acid, or sodium
bicarbonate proved to further facilitate this process, and 4-alkyl-
anisoles 17-28 and 34 were isolated with typical overall yields
diastereomer B (δ 3.06) provided enhancement of a single Tp
resonance. Additionally, for isomer 16B, irradiation of H4
resulted in enhancement of two imidazole signals. Stereoisomers
of 5-16 and 29-33 differing in configuration at the latent
benzylic position are designated as endo if the observed
stereochemical outcome presumably resulted from an endo
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Michael Addition with
η
2-Coordinated Anisoles
A R T I C L E S
ranging from 50 to 85% starting from the TpRe(CO)(RIm)-
(arene) complexes (Tables 1 and 2).
Discussion
The {TpRe(CO)(RIm)} metal fragments bind an anisole
preferentially across C5-C6, rendering the π-bonds of the
uncoordinated portion of the arene ligand partially localized.
Due to the electron-donating properties of the methoxy group,
the π-system is polarized so that the most nucleophilic positions
are C2 and C4. However, the approach to C2 is hindered by
the methoxy group, which must lie in the plane of the ring, but
away from the metal. Thus, the addition of Michael-type
electrophiles is observed only at C4. This regiochemistry is
consistent with that observed for Michael reactions of pentaam-
mineosmium(II)(η2-anisole) complexes.16
Michael additions of pentaammineosmium(II)(η2-anisole)
complexes were successfully performed, but under more acidic
conditions using HOTf in acetonitrile as a promoter. Similar
conditions were ineffective with the second-generation {TpRe-
(CO)(RIm)} anisole complexes, presumably because these
rhenium fragments are more susceptible to oxidation of the metal
center. This study of TpRe(CO)(RIm)(η2-anisole) complexes
has shown that the arene ligand is more activated toward
electrophilic addition than that of the pentaammineosmium(II)
analogues,24,26 though also more easily oxidized by acid. This
greater degree of arene activation is manifested by the ability
to promote Michael additions using acids that are nearly 11
orders of magnitude weaker than those utilized with pentaam-
mineosmium(II) (∼pKa -10 for CH3CNH+ vs ∼pKa 0.8 for
Ph2NH2+). Given the observed disparity in the results of {TpRe-
(CO)(MeIm)} anisole reactions promoted with water and Sc-
(OTf)3 and those attempted with anhydrous Sc(OTf)3, it is
possible that in the synthesis of anisoliums 5-16, the lanthanide
salt/water combination functioned primarily as a proton source.
Michael addition reactions with TpRe(CO)(RIm)(η2-anisole)
occur with control of up to three stereogenic centers (counting
the two bound carbons as a single stereocenter). While the parent
arene complexes (1-4) typically exhibit low facial diastereo-
selectivity in equilibrated solutions (2:1 ratio of A:B), both the
TpRe(CO)(RIm)(arene) complexes and their conjugate acids
have been observed in significantly higher (up to >20:1)
diastereomeric ratios.29 Spectroscopic data of solutions generated
at low temperature (-40 to -80 °C) have conclusively
demonstrated that {TpRe(CO)(L)} arene complexes in the solid
state exist as much higher ratios of coordination diastereomers
than are typically observed in solutions at ambient temperature.30
It is thought that under the reaction conditions used in the
synthesis of anisolium complexes 29-33, TpRe(CO)(BuIm)-
(5,6-η2-anisole) (4) is protonated at a rate much greater than
that at which coordination isomerizations of the arene ligand
occur. The resulting anisolium species is a stronger π-acid than
the initial arene, and both substitution and isomerization rates
are expected to be dramatically reduced. Thus, the diastereo-
selectivity that is initially present in the solid state is trapped in
solution by rapid protonation (Scheme 2).30 Since a high degree
of facial diastereoselectivity (A:B) is observed in Michael
adducts 29-33, it is reasonable to conclude that, upon depro-
Figure 2. Transition state representations for the acid-catalyzed Michael
addition of TpRe(CO)(MeIm)(5,6-η2-(3-methylanisole)) (2) to 3-penten-2-
one.
tonation of the anisolium, reaction of 4 with the Michael
acceptor is also a much faster process than the facial isomer-
izations of the arene ligand. 4H-Anisolium complexes having a
high degree of facial diastereoselectivity are therefore formed
from samples of TpRe(CO)(BuIm)(5,6-η2-anisole) (4), which
exist in high diastereomeric ratios carried over from the solid
state (see Scheme 2).30
The addition of a carbon electrophile to C4 of TpRe(CO)-
(RIm)(anisole) complexes generates a stereogenic center at this
position. Consistent with all previous examples of electrophilic
additions to TpRe(CO)(L)(naphthalene) and pentaammineosmium-
(II) arene complexes,17,31 the Michael acceptors approach the
bound arenes exclusively from the unbound arene face, selec-
tively setting the stereochemistry at C4. Evidence for this
pathway includes the observed NOE effect on imizadole signals
upon irradiation of the H4 proton of [TpRe(CO)(MeIm)(4â-(2-
(methoxycarbonyl)ethyl)-5R,6R-η2-(4H-anisolium))](OTf) (16B)
(vide supra).
When â-substituted Michael acceptors react with a bound
anisole, a stereogenic center is formed at the latent benzylic
position (formally C1′ for all anisolium complexes except 14
and 15, for which this position is designated as C4′). The high
stereoselectivity observed [Tables 1 and 2, dr (endo:exo)]
suggests the presence of an ordered transition state. Figure 2
shows two possible reaction pathways for the acid-catalyzed
Michael addition of TpRe(CO)(MeIm)(5,6-η2-(3-methylanisole))
(2) to 3-penten-2-one. On the left, (i) is a transition state
(29) Valahovic, M. T.; Gunnoe, T. B.; Sabat, M.; Harman, W. D. J. Am. Chem.
Soc. 2002, 124, 3309-3315.
(30) Keane, J. M.; Ding, F.; Sabat, M.; Harman, W. D. J. Am. Chem. Soc. 2003,
126, 785-789.
(31) Valahovic, M. T.; Keane, J. M.; Harman, W. D. In Modern Arene
Chemistry; Astruc, D., Ed.; Wiley-VCH Verlag GmbH & KGaA: Wein-
heim, 2002, pp 297-329.
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A R T I C L E S
Smith et al.
Scheme 3. Diels-Alder Reaction of
between methyl groups is negligible for the purported endo-
approach and the dr is again high (10:1). In addition to the steric
factor, a methyl group situated at the 3-position of the bound
anisole can stabilize the competing open transition state through
hyperconjugation. A direct electrophilic addition at C4 would
result in some 4H-anisolium character in the transition state and,
therefore, a buildup of positive charge at C3.
TpRe(CO)(MeIm)(5,6-η2-anisole) (1) and Retro-Aldol Ring Opening
of the Resulting Cycloadduct (35)
The high stereocontrol of the latent benzylic carbon afforded
by these rhenium anisole complexes is typically not realized in
the analogous osmium(II) chemistry. Whereas reactions with
the TpRe(CO)(RIm)(η2-anisole) complexes are likely to be
influenced by orbital interactions (vide supra), Michael reactions
that were carried out with pentaammineosmium(II) anisole
complexes required highly acidic reaction conditions and likely
have open transition states that are dominated by charge-charge
interactions. In the original pentaammineosmium(II)(η2-anisole)
study with Michael acceptors, triflic acid in acetonitrile was
required for the reactions to occur. Due to low thermal stability
of the resulting 4H-anisolium species, rearomatized 4-alkylated
anisole complexes were isolated.16 While high diastereoselec-
tivities were observed for these complexes, a follow-up study
utilizing a remote chiral center39 showed this stereoselectivity
to be the result of linkage isomerizations of the metal fragment,
after the Michael addition. The selectivity in the Michael
reaction itself was found in most cases to be poor.39
resembling that for an endo-Diels-Alder reaction, which would
lead to 9 with predictable stereocontrol at the latent benzylic
carbon (labeled with an asterisk). Conversely, the open transition
state ii would not be expected to afford high stereoselectivity
at this position.
In a recent communication,24 it was reported that TpRe(CO)-
(MeIm)(η2-benzene) undergoes an endo-selective Diels-Alder
reaction with NMM to generate the corresponding endo-adduct
exclusively. In a similar manner, TpRe(CO)(MeIm)(5,6-η2-
anisole) (1) reacts to form a cycloadduct, isolated as two
coordination diastereomers, in which the methoxy group is in
a bridgehead position (Scheme 3). The isomer arising from
coordination diastereomer 1A (35A) was separated from 35B
by chromatography and then treated with TBSOTf in the
presence of TFA to afford a sample of anisolium complex 14A
with identical stereochemistry to that generated by the acid-
catalyzed Michael addition pathway (1H NMR).
For Michael addition reactions involving TpRe(CO)(MeIm)-
(5,6-η2-anisole) (1), the hypothesized Diels-Alder-like reaction
pathway in Figure 2 is most consistent with the high stereose-
lectivity observed at the latent benzylic carbon. A similar
explanation has been invoked with highly diastereoselective
Mukaiyama Michael32,33 and Mukaiyama aldol34-36 reactions.
In contrast, Michael reactions with TpRe(CO)(MeIm)(5,6-η2-
(3-methylanisole)) (2), which show poor stereocontrol, are likely
to proceed through the more conventional open transition state
(ii), typical of a standard Mukaiyama Michael addition.37,38 The
presence of the additional methyl group in 2 is expected to
disfavor a Diels-Alder-like reaction pathway in two ways. The
3-methyl substituent should cause steric strain in the endo
transition state for cis, but not trans, substituted Michael
acceptors. Thus, the Michael addition of 1 to cyclohexenone
(Table 1, item 6) yields a dr of >20:1 (endo/exo), whereas the
analogous addition of the 3-methyl analogue (2; Table 1, item
7) affords a dr of only 1:1. However, when the trans-substituted
olefin 3-penten-2-one (Table 1, item 9) is used, the steric strain
In special cases, success in controlling the stereochemistry
of the benzylic position has been realized using pentaammin-
eosmium(II). A reaction with N-methylmaleimide and [Os-
(NH3)5(η2-anisole)]2+ in the presence of BF3‚OEt2 gave the
corresponding 4H-anisolium complex.40 Under kinetic condi-
tions, this anisolium was shown to cyclize to give a bicyclooc-
tadiene complex having endo-stereochemistry similar to 35. Yet,
the possibility of linkage isomerizations occurring after the
Michael addition could not be excluded, so the final orientation
of the cycloadduct did not provide strong evidence of selectivity
in the initial addition reaction. Also relevant to this discussion
are conjugate addition reactions reported for phenol complexes
of pentaammineosmium(II).15,41 In contrast to the osmium-
anisole Michael reactions, those with phenol were carried out
under mildly basic reaction conditions. The isolated 4-substituted
dienone products showed a high degree of diastereoselectivity
at the latent benzylic carbon. While the putative cycloadduct
intermediate could not be isolated, the high dr was hypothesized
to result from the formation of an endo-selective Diels-Alder
cycloadduct intermediate.
With a viable strategy in hand to control the stereochemistry
of the organic ligand relative to that of the transition metal,
one could imagine controlling the absolute stereochemistry of
the 4H-anisolium ligand (and, thus, the 4-substituted anisole),
provided that the reaction sequence was carried out with an
enantio-enriched form of the rhenium. In a recent report, a
resolved form of TpRe(MeIm)(η2-benzene) was prepared using
R-pinene.42 However, the observation that a compound forms
a stereoselective solid phase as a racemic mixture does not
guarantee the same result for the corresponding enantio-enriched
(32) Evans, D. A.; Scheidt, K. A.; Johnston, J. N.; Willis, M. C. J. Am. Chem.
Soc. 2001, 123, 4480-4491.
(33) Talan, L. A.; Poon, C. D.; Evans, S. A. J. J. Org. Chem. 1996, 61, 7455-
7462.
(34) Danishefsky, S. J.; Larson, E.; Askin, D.; Kato, N. J. Am. Chem. Soc. 1985,
107, 1246-1255.
(35) Birkinshaw, T. N.; Tabor, A. B.; Holmes, A. B.; Kaye, P.; Mayne, P. M.;
Raithby, P. R. J. Chem. Soc. Chem. Commun. 1988, 1599-1601.
(36) Birkinshaw, T. N.; Tabor, A. B.; Holmes, A. B.; Raithby, P. R. J. Chem.
Soc. Chem. Commun. 1988, 1599-1601.
(39) Chordia, M. D.; Harman, W. D. J. Am. Chem. Soc. 2000, 122, 2725-
2736.
(40) Kopach, M. E.; Harman, W. D. J. Org. Chem. 1994, 59, 6506-6507.
(41) Kopach, M. E.; Harman, W. D. J. Am. Chem. Soc. 1994, 116, 6581-6592.
(42) Meiere, S. H.; Valahovic, M. T.; Harman, W. D. J. Am. Chem. Soc. 2002,
124, 15099-15103.
(37) Oare, D. H.; Heathcock, C. H. Top. Stereochem. 1991, 21, 227.
(38) Narasaki, K.; Soai, K.; Mukaiyama, T. Chem. Lett. 1974, 1223-1224.
9
15548 J. AM. CHEM. SOC. VOL. 126, NO. 47, 2004

Michael Addition with
η
2-Coordinated Anisoles
A R T I C L E S
resulting precipitate was collected on a fine frit, washed with hexanes
(3 × 1 mL), and dried in vacuo to yield a brown solid.
material. If the racemate organizes in a centrosymmetric space
group in the solid, this state will not be possible for the enantio-
enriched form. For example, consider the anisole complex 1,
which, despite its 2:1 equilibrium ratio, precipitates in hexanes
to form a solid containing >95% diastereomer A. When an
enantio-enriched sample of 1 was precipitated in the same
manner, protonation experiments showed the resulting solid to
contain only a 3:1 ratio of A:B.28,30 Thus, the present system
does not appear to not be amenable to the efficient preparation
of enantio-enriched para-alkylated anisoles.
The difficulty in effecting rearomatization of anisoliums 5-16
and 29-33 through simple deprotonation may be ascribed to
both the high degree of steric bulk surrounding the C4-proton
and the stabilization afforded the anisolium through π-electron
donation from the metal. The proton is blocked on one face by
the ligands of the metal center and on the other face by the
newly added alkyl chain of the Michael acceptor. In addition,
the greater π-electron donation involved in {TpRe(CO)(RIm)}
anisolium complexes makes these species significantly less
acidic than the analogous pentaammineosmium(II) anisoliums,
which are readily deprotonated by amine bases.16 It is speculated
that the stability of 5-16 and 29-33 to moderately strong bases
may allow for reactions of these anisolium complexes with
stronger nucleophiles than those that were employed with the
analogous pentaammineosmium(II) species.
Anisolium regiochemistry is designated by considering the metal to
be bound across C5 and C6. Facial diastereomers are designated as A
if the 1-position methoxy group is directed toward the imidazole ligand
and as B if the 1-position methoxy group is directed away from the
imidazole ligand. Stereiosomers designated as endo are those thought
to have resulted from an endo transition state arrangement of the
Michael acceptor with respect to the unbound portion of the aromatic
ring. The alternative configuration is designated as exo. The accuracy
of this designation is certain only for complex 14. Anisolium complexes
5-16 and 29-33 were unstable to purification on silica or alumina,
and attempts to crystallize the products were unsuccessful. Yields of
these complexes are reported only for those that were isolated in
analytically pure forms.
[TpRe(CO)(MeIm)(4â-(3-oxocyclopentyl)-5r,6r-η2-(4H-anisoliu-
m))](OTf) (10). Reaction time was 12 h. This compound was isolated
1
as a mixture of isomers in a ratio of 1:2 A:B and 16:1 endo:exo. H
NMR (acetone-d6, ambient temperature, δ): minor diastereomer (10A-
endo), 8.17 (1H, d, J ) 2.0, Tp 3,5), 8.11 (1H, buried, Tp 3,5), 7.99
(1H, d, J ) 2.0, Tp 3,5), 7.92 (1H, d, J ) 2.0, Tp 3,5), 7.84 (1H,
buried, Tp 3,5), 7.82 (1H, bs, Im), 7.47 (1H, d, J ) 2.0, Tp 3,5), 7.32
(1H, bs, Im), 7.18 (1H, m, H3), 6.70 (1H, d, J ) 9.9, H2), 6.58 (1H,
buried, Im), 6.55 (1H, buried, Tp 4), 6.36 (1H, t, J ) 2.0, Tp 4), 6.14
(1H, t, J ) 2.0, Tp 4), 4.57 (1H, d, J ) 7.4, H6), 4.21 (1H, d, J ) 7.4,
H5), 3.90 (3H, s, NCH3), 3.60 (1H, buried, H4), 3.57 (3H, s, OCH3),
2.56-1.46 (7H, several m, H1′, 2 × H2′, 2 × H4′, and 2 × H5′) (BH
not observed); minor diastereomer (10A-exo), 4.13 (1H, d, J ) 7.4,
H5); major diastereomer (10B-endo), 8.26 (1H, d, J ) 2.0, Tp 3,5),
8.11 (1H, d, J ) 2.0, Tp 3,5), 8.10 (1H, d, J ) 2.0, Tp 3,5), 7.83 (1H,
d, J ) 2.0, Tp 3,5), 7.54 (1H, d, J ) 2.0, Tp 3,5), 7.40 (1H, d, J ) 2.0,
Tp 3,5), 7.29 (1H, bs, Im), 7.01 (1H, ddd, J ) 10.6, 4.8, 1.6, H3), 6.75
(1H, bs, Im), 6.58 (1H, t, J ) 2.0, Tp 4), 6.55 (1H, bs, Im), 6.54 (1H,
buried, H2), 6.45 (1H, t, J ) 2.0, Tp 4), 6.15 (1H, t, J ) 2.0, Tp 4),
4.89 (1H, d, J ) 7.5, H5), 3.90 (3H, s, NCH3), 3.64 (1H, d, J ) 7.5,
H6), 3.37 (1H, m, H4), 3.06 (3H, s, OCH3), 2.56-1.46 (7H, several
m, H1′, 2 × H2′, 2 × H4′, and 2 × H5′) (BH not observed); minor
diastereomer (10B-exo), 4.82 (1H, d, J ) 6.7, H5). 13C NMR (acetone-
d6, ambient temperature, δ): minor diastereomer (10A-endo), 216.8
(C3′), 196.1 (CO), 187.3 (C1), 151.6 (C3), 144.6 (Tp 3,5), 144.2 (Tp
3,5), 143.1 (Tp 3,5), 141.1 (Tp 3,5), 138.5 (Tp 3,5), 138.0 (Tp 3,5),
136.2 (Im), 124.1 (Im), 123.8 (Im), 119.5 (C2), 108.1 (Tp 4), 107.7
(Tp 4), 107.4 (Tp 4), 67.2 (C5), 58.2 (OCH3 or C6), 57.7 (OCH3 or
C6), 48.8 (C4), 45.0 (C1′), 42.5 (C2′), 38.3 (C4′), 35.0 (NCH3), 27.9
(C5′); major diastereomer (10B-endo), 217.1 (C3′), 194.9 (CO), 186.2
(C1), 150.8 (C3), 148.2 (Tp 3,5), 144.3 (Tp 3,5), 142.2 (Tp 3,5), 140.9
(Tp 3,5), 139.2 (Tp 3,5), 137.8 (Tp 3,5), 136.9 (Im), 130.1 (Im), 124.0
(Im), 123.6 (C2), 109.0 (Tp 4), 108.2 (Tp 4), 107.5 (Tp 4), 69.4 (C5),
59.3 (C6), 58.0 (OCH3), 50.0 (C4), 43.7 (C1′), 42.1 (C2′), 38.5 (C4′),
35.0 (NCH3), 26.8 (C5′). IR: νBH ) 2496 cm-1 (vw), νCtO ) 1852
cm-1 (s), νCdO ) 1704 cm-1 (s). CV: Ep,a ) 1.05 V, Ep,c ) -1.00 V.
Anal. Calcd for C27H31BF3N8O6ReS: C, 38.17; H, 3.68; N, 13.33.
Found: C, 37.84; H, 3.34; N, 13.33.
Experimental Section
General Methods. Unless otherwise noted, all synthetic reactions
and electrochemical experiments were performed under a dry nitrogen
atmosphere. Preparative thin-layer chromatography (TLC) was per-
formed on Uniplate silica gel GF or alumina GF plates from Analtech
Inc. CH2Cl2, benzene, tetrahydrofuran (THF), and hexanes were purged
with nitrogen and purified by passage through a column packed with
activated alumina.43 Other solvents and liquid reagents were thoroughly
purged with nitrogen prior to use. Deuterated solvents were used as
received from Cambridge Isotopes. Compounds TpRe(CO)(MeIm)(η2-
benzene),20,21,24 1,21 2,24 3,24 4,24 17,16 20,16 22,44 24,16,44 26,44 27,16 and
35,24 have been previously reported.
General Procedure for TpRe(CO)(RIm)(η2-anisole) Complexes
1-4. The anisole complexes were prepared using the procedure of
Meiere. 21 In a typical procedure, TpRe(CO)(RIm)(η2-benzene) (1.2 g,
2 mmol) is dissolved in THF (∼5 mL), and then the solution is diluted
with the desired anisole (10 mL) and stirred 72 h at 25 °C. The resulting
precipitate is collected on a fine frit, washed with hexanes (3 × 5 mL),
and dried in vacuo. Typical yields are >85%.
Compounds 5-15 were synthesized as follows: Two solutions,
the first consisting of a {TpRe(CO)(MeIm)} anisole complex (1.0 ×
10-4 mol) and a Michael acceptor (5.0 × 10-4 mol) dissolved in CH2-
Cl2 (4.4 g) and the second consisting of Sc(OTf)3 (1.1 × 10-4 mol)
dissolved in THF and water (6.0 mL of a 1.6% v/v solution of water
in THF), were chilled to -10 °C and then combined. An immediate
color change from pale yellow to dark red/orange was observed. The
reaction was monitored by recording an infrared spectra of aliquots of
the reaction treated with pyridine (Re-anisole νCtO ) 1797 cm-1). When
all the starting material was consumed, the reaction mixture was
transferred to a round-bottomed flask, and volatiles were removed under
reduced pressure. The resulting residue was rinsed with ∼1:1 Et2O/
hexanes (3 × 10 mL), dissolved in DME (∼3 mL), and added to a
stirring solution of hexanes/Et2O (100 mL, 1:1). The solution was chilled
for ∼5 min by solvent evaporation under reduced pressure, and the
Compound 16. Two solutions, the first consisting of TpRe(CO)-
(MeIm)(5,6-η2-anisole) (1, 0.06 g, 1 × 10-4 mol) and methylacrylate
(0.09 g, 1 × 10-3 mol, predried by passing through a plug of anhydrous
alumina or by stirring with activated alumina then filtering) dissolved
in CH2Cl2 (4.4 g) and the second consisting of TBSOTf (0.029 g, 1.1
× 10-4 mol, predried by passing through a plug of anhydrous alumina)
dissolved in CH2Cl2 (0.5 g), were chilled to -40 °C and combined.
An immediate color change was observed from pale yellow to dark
red/orange. The reaction was monitored by electrochemistry or IR (1;
νCtO ) 1797 cm-1) with the IR aliquot being first quenched with base
(TEA, DIEA, or NH3/MeOH). When all the starting material was
consumed (∼20 min), cold (-40 °C) methanol (0.5 mL) was added
and the reaction was stirred for an additional 10 min. The reaction
(43) Pangborn, A. B.; Giardello, M. A.; Grubbs, R. H.; Rosen, R. K.; Timmers,
F. J. Organometallics 1996, 15, 1518-1520.
(44) Jones, P.; Reddy, C. K.; Knochel, P. Tetrahedron 1998, 54, 1471-1490.
9
J. AM. CHEM. SOC. VOL. 126, NO. 47, 2004 15549

A R T I C L E S
Smith et al.
mixture was transferred to a round-bottomed flask, and volatiles were
removed under reduced pressure. The residue was rinsed with hexanes
(3 × 10 mL). The remaining red oil was dissolved in DME (∼3 mL)
and added to a stirring solution of hexanes/Et2O (100 mL, 1:1). The
mixture was chilled by applying a vacuum for ∼5 min, and the resulting
precipitate was collected on a fine frit, washed with hexanes (3 × 1
mL), and dried under vacuum.
sulfate (5 g), and the resulting mixture was stirred for 1 h. The solid
portion was removed by filtration and rinsed with benzene (4 mL).
The filtrate was added to stirring hexanes (100 mL) using a benzene
(1 mL) rinse. The resulting mixture was stirred until the solution portion
was completely transparent. The solution portion was then removed
by decantation, and the remaining material was dissolved in methylene
chloride (1 mL). To this solution was added benzene (4 mL), and the
resulting solution was added to stirring hexanes to give a precipitate
that was collected by filtration, rinsed with hexanes, and dried in vacuo
to give a tan solid.
[TpRe(CO)(MeIm)(4â-(2-(methoxycarbonyl)ethyl)(5r,6r-η2-(4H-
anisolium))](OTf) (16). This compound was isolated as a 1:1 mixture
of 16A and 16B. 1H NMR (acetone-d6, ambient temperature, δ): 16A,
8.13 (2H, d, J ) 2.0, 2 × Tp 3,5), 7.98 (1H, d, J ) 2.0, Tp 3,5), 7.86,
(1H, bs, Im), 7.82 (2H, d, J ) 2.0, 2 × Tp 3,5), 7.46 (1H, d, J ) 2.0,
Tp 3,5), 7.31 (1H, bs, Im), 7.18 (1H, ddd, J ) 9.7, 4.8, 1.8, H3), 6.65
(1H, d, J ) 10.2, H2), 6.6 (1H, buried, Im), 6.56 (1H, t, J ) 2.0, Tp
4), 6.36 (1H, t, J ) 2.0, Tp 4), 6.16 (1H, t, J ) 2.0, Tp 4), 4.51 (1H,
ddd, J ) 7.5, 1.8, 1.8, H6), 4.05 (1H, ddd, J ) 7.5, 1.6, 1.6, H5), 3.92
(3H, s, NCH3), 3.58 (3H, s, COOCH3), 3.55 (3H, s, 1-pos OCH3), 3.56
(1H, b, H4), 2.4-2.2 (2H, m, H2′), 1.8-2.2 (2H, m, H1′) (BH not
observed); 16B, 8.26 (1H, d, J ) 2.0, Tp 3,5), 8.11 (1H, d, J ) 2.0,
Tp 3,5), 8.09 (1H, d, J ) 2.0, Tp 3,5), 8.03 (1H, bs, Im), 7.83 (1H,
buried, Tp 3,5), 7.54 (1H, d, J ) 2.0, Tp 3,5), 7.35 (1H, d, J ) 2.0, Tp
3,5), 7.28 (1H, bs, Im), 6.99 (1H, ddd, J ) 9.8, 4.8, 1.8, H3), 6.67
(1H, bs, Im), 6.59 (1H, t, J ) 2.0, Tp 4), 6.51 (1H, buried, H2), 6.46
(1H, t, J ) 2.0, Tp 4), 6.16 (1H, t, J ) 2.0, Tp 4), 4.83 (1H, ddd, J )
7.7, 1.7, 1.6, H5), 3.91 (3H, s, NCH3), 3.62 (3H, s, COOCH3), 3.56
(1H, buried, H6), 3.33 (1H, m, H4), 3.06 (3H, s, OCH3), 2.4-2.2 (2H,
m, H2′), 1.8-2.2 (2H, m, H1′) (BH not observed). 13C (acetone-d6,
ambient temperature, δ): 16A (select resonances), 196.2 (CO), 187.7
(C1), 173.8 or 173.6 (COOCH3, other is 16B COOCH3), 153.0 (C3),
68.7 (C5), 51.7 (COOCH3), 43.8 (C4). (16B) 195.1 (CO), 186.3 (C1),
173.8 or 173.6 (COO CH3, other is 16A COO CH3), 151.8 (C3), 71.3
(C5), 51.7 (COO CH3), 45.2 (C4). IR: νCtO ) 1853 cm-1 (vs), νCdO
) 1728 cm-1 (s). CV: Ep,a ) 1.09 V, Ep,c ) -1.02 V. Anal. Calcd for
C26H31BF3N8O7ReS: C, 36.58; H, 3.66; N, 13.13. Found: C, 36.77;
H, 3.66; N, 13.23.
[TpRe(CO)(BuIm)(4â-(3-oxobutyl)-5r,6r-η2-(4H-anisolium))]-
(OTf) (29). MVK (3.17 × 10-4 mol) was used in the synthesis of this
compound. It was isolated as a >20:1 mixture of 29A and 29B (89.2%).
1H NMR (acetone-d6, ambient temperature, δ): major diastereomer
(29A), 8.13 (2H, d, J ) 2.1, 2 × Tp 3,5), 7.99 (1H, d, J ) 2.4, Tp
3,5), 7.83 (1H, d, J ) 2.4, 2 × Tp 3,5), 7.82 (1H, very broad, Im),
7.41 (1H, d, J ) 2.4, Tp 3,5), 7.40 (1H, t, J ) 1.5, Im), 7.20 (1H, ddd,
J ) 9.9, 5.1, 2.1, H3), 6.64 (1H, very broad, Im), 6.63 (1H, ddd, J )
9.9, 1.5, 1.5, H2), 6.56 (1H, t, J ) 2.4, Tp 4), 6.36 (1H, t, J ) 2.4, Tp
4), 6.17 (1H, t, J ) 2.4, Tp 4), 4.7 (1H, very broad, BH), 4.54 (1H, d,
J ) 7.8, H6), 4.22 (2H, t, J ) 7.2, NCH2), 4.10 (1H, d, J ) 7.5, H5),
3.60 (3H, s, OCH3), 3.53 (1H, m, H4), 2.51 (2H, m, H2′), 2.01 (3H, s,
H4′), 1.92, (2H, m, H1′), 1.79 (2H, m, NCH2CH2), 1.26 (2H, m, CH2-
CH3), 0.90 (3H, t, J ) 7.5, CH2CH3); minor diastereomer (29B), 8.24
(1H, d, J ) 2.1, Tp 3,5), 8.12 (1H, buried, Tp 3,5), 8.09 (1H, d, J )
2.7, Tp 3,5), 8.01 (1H, bs, Im), 7.54 (1H, d, J ) 2.1, Tp 3,5), 7.36
(1H, bs, Im), 7.31 (1H, d, Tp 3,5), 6.99 (1H, ddd, J ) 9.9, 5.1, 2.1,
H3), 6.73 (1H, bs, Im), 6.59 (1H, t, J ) 2.1, Tp 4), 6.48 (1H, buried,
H2), 6.46 (1H, t, J ) 2.4, Tp 4), 6.17 (1H, buried, Tp 4), 4.81 (1H, d,
J ) 7.5, H5), 3.59 (1H, buried, H6), 3.29 (1H, m, H4), 3.06 (3H, s,
OCH3), 2.51 (2H, buried, H2′), 2.01 (3H, buried H4′), 1.92 (2H, buried,
H1′) (1 × Tp 3,5, BH, NCH2, NCH2CH2, CH2CH3, and CH2CH3 buried
or otherwise indiscernible). 13C NMR (acetone-d6, ambient temperature,
δ): major diastereomer (29A), 207.6 (C3′), 196.1 (CO), 187.9 (C1),
153.6 (C3), 144.4 (Tp 3,5), 143.9 (Tp 3,5), 143.0 (Tp 3,5), 138.5 (Tp
3,5), 138.0 (Tp 3,5), 136.2 (Tp 3,5), 131.6 (Im), 123.9 (C2), 121.8
(Im), 121.0 (Im), 108.1 (Tp 4), 107.7 (2 × Tp 4), 69.2 (C5), 59.0
(OCH3), 57.4 (C6), 48.5 (NCH2), 44.0 (C4), 40.1 (C2′), 33.3 (NCH2CH2),
32.2 (C1′), 29.8 (buried, C4′), 20.0 (CH2CH3), 13.6 (CH2CH3). IR: νCt
Compounds 17-28 were synthesized from compounds 5-16 as
follows: The anisolium complex (1.5 × 10-4 mol) was combined with
CuBr2 (1.8 × 10-4 mol) in a vial with a magnetic stir bar. Acetone
(∼5 mL) was added, and the reaction was stirred open to air for 30
min. The mixture was added dropwise to stirring hexanes (100 mL),
and the resulting cloudy solution was stirred vigorously until clear.
The supernatant was collected, filtered through a medium frit, and
concentrated under reduced pressure to afford the crude product. The
product was purified by preparatory thin-layer chromatography using
hexanes/EtOAc as the eluent.
) 1852 cm-1 (vs), νBH ) 2497 cm-1 (w), νCdO ) 1710 cm-1 (s).
O
CV: Ep,a ) 1.18 V (II/I), Ep,c ) -1.04 V. Anal. Calcd for C29H37-
BF3N8O6ReS: C, 39.59; H, 4.24; N, 12.74. Found: C, 39.43; H, 4.23;
N, 12.72.
Conclusion
Compounds 17, 20, 22, 24, and 34 were synthesized from
compounds 29-33 as follows: The anisolium complex (0.100 g) was
combined with CuBr2 (0.038 g) and sodium bicarbonate (0.030 g) in a
vial with a magnetic stir bar. Acetonitrile (∼4 mL) was added, and the
reaction was stirred for 60 min. Volatiles were removed by rotary
evaporation, and the remaining residue was taken up in chloroform
and added to stirring hexanes (100 mL). The resulting mixture was
filtered. Volatiles were removed from the filtrate by rotary evaporation,
and the remaining colorless residue was purified by preparatory thin-
layer chromatography using hexanes/EtOAc as the eluent.
The {TpRe(CO)(RIm)(anisole) complexes 1-4 undergo
Michael addition reactions with a variety of R,â-unsaturated
carbonyl compounds under mild conditions to diastereoselec-
tively afford anisolium products substituted exclusively at C4.
The high degree of stereoselectivity observed in these reactions
is attributed to the trapping of a single coordination diastereomer
found in solid samples of TpRe(CO)(RIm)(arene) complexes
and to a Diels-Alder-like transition state for the Michael
reaction. Anisolium complexes 5-16 and 29-33 are surpris-
ingly stable and resistant to rearomatization. They may be
isolated and manipulated at 25 °C under an inert atmosphere
without degradation. However, rearomatization and decomplex-
ation may be accomplished by oxidation of the Re(I) center to
afford net aromatic substitution products in moderate overall
yields. When compared to the analogous pentaammineosmium-
(II) systems, the TpRe(CO)(RIm)(anisole) complexes show
dramatically increased reactivity, undergoing Michael addition
reactions under mild conditions with greater stereocontrol at
the benzylic position. While the present system is not suitable
Except where otherwise noted, compounds 29-33 were synthe-
sized as follows: To a mixture of TpRe(CO)(BuIm)(5,6-η2-anisole)
(4, 0.100 g, 1.52 × 10-4 mol) and diphenylammonium triflate (0.100
g, 3.13 × 10-4 mol) at -40 °C was added a solution of a Michael
acceptor (1.52 × 10-3 mol) in acetonitrile (0.5 g) at -40 °C. The
resulting yellow mixture was stirred at -40 °C for ∼48 h, during which
time it became a deep red solution. Brine (5 mL) and benzene (5 mL)
were then added, and the resulting mixture was shaken vigorously at
ambient temperature. The top layer (dark brown, organic) was removed,
and the remaining (aqueous) portion was extracted once more with
benzene (1 mL). To the combined organic portions was added sodium
9
15550 J. AM. CHEM. SOC. VOL. 126, NO. 47, 2004

Michael Addition with
η
2-Coordinated Anisoles
A R T I C L E S
for controlling the absolute stereochemistry of the Michael
addition products, this study demonstrates how the solid state30,45
can impact the stereochemistry of organic transformations with
η2-coordinated arenes.
of this research (ACS-PRF#36638-AC1). This work was also
supported by the NSF (CHE0111558 and 9974875) and the NIH
(NIGMS: R01-GM49236).
Supporting Information Available: Synthetic procedures and
detailed characterization data. This material is available free of
charge via the Internet at http://pubs.acs.org.
Acknowledgment is made to the donors of the Petroleum
Research Fund, administered by the ACS, for partial support
(45) Smith, P. L. Ph.D. Dissertation; University of Virginia, Charlottesville, VA,
2002, pp 160-161.
JA047054J
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J. AM. CHEM. SOC. VOL. 126, NO. 47, 2004 15551